Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals.
Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals.
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DOI：
10.1111/j.1753-4887.2011.00394.x
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发表时间：
2011-06
影响因子：
6.1
通讯作者：
Hwang DH
中科院分区：
文献类型：
--
作者：
Zhao L;Lee JY;Hwang DH
新的证据表明，模式识别受体（PRR）、Toll样受体（TLR）和核苷酸结合寡聚结构域蛋白（NOD）分别通过识别病原体相关分子模式和内源性分子来介导感染诱导的炎症和无菌性炎症。 PRR 介导的慢性炎症是癌症、动脉粥样硬化和胰岛素抵抗等慢性疾病发生和进展的决定因素。最近的研究表明，某些植物化学物质可抑制 PRR 介导的促炎症。姜黄素、海伦醛、肉桂醛和萝卜硫素分别含有 α、β-不饱和羰基或异硫氰酸酯基团，已知它们与半胱氨酸残基中的游离 SH 基团相互作用，但不与白藜芦醇（不含不饱和羰基）相互作用，通过干扰 TLR4 受体二聚化来抑制 TLR4 活化。同样，姜黄素以及小白菊内酯和海伦醛（但白藜芦醇和 EGCG 除外）也通过干扰 NOD2 二聚化来抑制 NOD2 活化。相比之下，白藜芦醇、EGCG、木犀草素和木犀草素的结构类似物通过靶向 TRIF 复合物中的 TBK1 和 RIP1 特异性抑制 TLR3 和 TLR4 信号传导。总之，这些结果表明 PRR 和下游信号成分是饮食策略的分子靶标，可减少 PRR 介导的慢性炎症和随之而来的慢性疾病风险。
Emerging evidence reveals that pattern-recognition receptors (PRR), Toll-like receptors (TLR) and Nucleotide-binding oligomerization domain proteins (NOD) mediate both infection-induced and sterile inflammation by recognizing pathogen-associated molecular patterns and endogenous molecules, respectively. PRR-mediated chronic inflammation is a determinant for the development and progression of chronic diseases including cancer, atherosclerosis and insulin resistance. Recent studies demonstrated that certain phytochemicals inhibit PRR-mediated pro-inflammation. Curcumin, helenalin, cinnamaldehyde and sulforaphane, containing α, β-unsaturated carbonyl or isothiocyanate group, respectively, that are known to interact with free SH groups in cysteine residues, but not resveratrol (with no unsaturated carbonyl group), inhibit TLR4 activation by interfering with TLR4 receptor dimerization. Similarly, curcumin, as well as parthenolide and helenalin, but not resveratrol and EGCG, also inhibits NOD2 activation by interfering with NOD2 dimerization. In contrast, resveratrol, EGCG, luteolin and structural analogs of luteolin, specifically inhibit TLR3 and TLR4 signaling by targeting TBK1 and RIP1 in TRIF complex. Together, these results suggest that PRRs and downstream signaling components are molecular targets for dietary strategies to reduce PRR-mediated chronic inflammation and consequent risks of chronic diseases.